The proposed work intends to advance our understanding of electrogenesis in cardiac pacemaker cells. Experiments will be performed on isolated preparations of cardiac Purkinje fibers to determine the ionic events responsible for the phenomenon of automaticity. Particular attention will be focused on the role of calcium in this process. Potentiometric techniques employing glass microelectrodes will be used to measure membrane potential. Various experimental conditions including "overdrive" stimulation, catecholamine application and glycoside toxicity will be used to study the specific relationship between calcium and the electrical variables determining pacemaker activity, i.e., maximum diastolic potential, threshold potential and rate of spontaneous diastolic depolarization. A mathematical model will be developed from these data which we hope will provide a unifying hypothesis useful for future study. Additionally, the proposed investigations may improve our understanding of cellular mechanisms of chronotropic receptor activity and of digitalis toxicity.